1. The Subject of the Invention
The present invention concerns non-mucin type synthetic compounds which were linked to carrier, that is, non-mucin type synthetic compounds or it's carrier conjugated compounds. The present invention further concerns the use of non-mucin type synthetic compounds or it's carrier conjugated compounds for preparation of monoclonal antibodies, human immunodeficiency virus (HIV) agents, antitumor agents and immunostimulants.
2. Current Technology
Mucin type antigens such as Tn (GalNAc α 1→O-Ser/Thr), TF (Gal β 1→3GalNAc α 1→O-Ser/Thr), STn (NeuAc α 2→6GalNAc1→O-Ser/Thr) as shown in following below figure, are highly expressed in tumor tissues, and appearance in the nomal tissues are restricted. (G. F. Springer, J. Natl, Cancer Inst., 1975, 54, 335., S. Hakomori, Advanced in Cancer Research, 1989, 52, 257) 
Recentry, Tn and STn epitopes, were found on the gp120 as human immunodeficiency virus (HIV) specific glycoprotein. (Hanse, J. E., J. Viol.; 1990, 64, 2833., J. Viol., 1991, 65, 6416.; Arch. Viol., 1992, 126, 11.) And it was reported that the monoclonal antibodies for the O-linked oligosaccharide block HIV infections. (Hanse, J. E., J. Viol.; 1990, 64, 2833.; Kumar A., Virology, 2000, 274, 149.)
The administration of mucin type tumor antigens and/or attached to pharmaceutically acceptable carriers are expected as a specific immunotherapy for cancer and HIV. Wherein these carriers are pharmaceutically acceptable proteins such as albumine (ALB), Keyhole limpet hemocyanin (KLH), BCG, or synthetic compounds such as palmitoyl derivatives, aromatic compounds, aliphatic compounds, alkyl, aminoalkyl, peptide and peptoid, which can obtain induction of immune response. (S. J. Danishefsky, J. Am. Chem. Soc. 1998, 120, 12474.; G. Ragupathi, Glycoconjugate J., 1998, 15, 217.; B. M. Sandmeier, J. Immunotherapy, 1999, 22(1), 54.; A. Singhal, Cancer Res., 1991, 51, 1406.; T. Shimizu, 1987, 55, 2287-2289.)
However, above mentioned mucine type antigens-carrier have O-glycoside linkage between sugar and carrier moiety. Therefore, considering about their metabolic stability and immunogenicity, these O-glycoside linkage are susceptible to hydrolyze by glycosidase such as N-acetyl galactosaminidase (EC 3.2.1.49) (Eq A), or hydrolyze of peptide bond by peptidase,as shown in following equation (Eq B), and their activities are anticipated to decrease or attenuate. 
On the other hand, Beau et al have been synthesized the C-glycosides (GalNAc α 1→CH2-Ser) that have the carbon atom instead of the oxygen atom which connect with serine and N-acetyl galactosamine as a metabolically stable Tn antigen, shown in following equation (A). This Tn antigen is stable against glycosidase such as N-acetyl galactosaminidase (Beau et al, J. C. S. Chem. Commun., 1998, 955.). But, when these C-glycosides are attached to peptides, these compounds could be hydrolyzed by peptidases, and their stabilities are not satisfactory in a living body. 
And Roy et al have been synthesized the glycopeptoids as the metabolic stable mimic of carbohydrate antigen, which was attached to peptoid that is metabolically stable against hydrolysis by peptidase, as shown in following equation (Tetrahedron Lett., 1997, 38, 3487.). But, his reported compounds are thought to be unstable, because it is also expected to be hydrolyzed by glycosidases such as N-acetyl galactosaminidase.
Beau and Roy have not reported to pharmacological activities of Tn antigen linked to carrier proteins. 
As mentioned above, the compound, prepared from a coupling of the precedented naturally occuring mucin type antigen and the carrier, is hydrolyzed at it's glycoside bond by glycosidase which exists widely in a living body and at it's peptide bond by peptidase. Therefore it is expected to obtain an insufficient effect.
3. The Subject of Invention
Under these situations, this invention was attained to solve these problems. The purposes of this invention are to prepare the non-mucin type synthetic compounds-carrier conjugated compounds which are stable to hydrolyze against both enzymes, glycosidase and peptidase.
And to prepare non-mucin type synthetic compounds-carrier conjugated compounds which have the ability of specific reactivity to induce immune response for cancer and HIV and have excellent active immunization activities.
And to prepare non-mucin type synthetic compounds-carrier conjugated compounds which are able to obtain selective monoclonal antibodies for cancer and HIV.
And to prepare anti-tumor agents, anti-HIV agents and immunostimulants which contain this non-mucin type synthetic compounds-carrier conjugated compounds as active ingredients.
And the method to prepare N-acetyl galactosamine in cost effectively, starting material of non-mucin type synthetic compounds-carrier conjugated compounds, is the another object of present invention.
4. A Solution of the Problem
Under these backgrounds, we maked effort to consider to prepare the metabolic stable compounds, having C-glycoside and peptoid, against to glycosidase and peptidase and the non-mucin compound as shown in following figure, were synthesized for the first time. These compounds are, so to speak, C-glycopeptoid and new compounds. 
These C-glycopeptoids are more metabolically stable against glycosidase and peptidase than known vaccines. Furthermore, they are able to show their effects for longer time and to store for long term at room temperature. When these novel C-glycopeptoids which are attached to pharmaceutically acceptable carrier proteins, these compounds are more metabolically stable in a living body than known vaccines against glycosidase and peptidase and also expected to show the excellent active immunization activities. It is expected that these novel C-glycopeptoids have potent passive immunogenicities for cancer and HIV. Monoclonal antibodies which were prepared using these compounds are expected to have activities for cancer therapy as a possive immune response. And these compounds have antitumor, anti HIV activity and immunopotentiation.
As a result of investigation of novel compounds as anti HIV agents and immunostimulant, the antibodies which was prepared using novel compound have excelent antitumor, anti HIV activity and immunostimulaion as shown in general formura (1).